Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors.
Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors.
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异种移植肿瘤中花青 7 标记甘露糖对肿瘤相关巨噬细胞的靶向成像
DOI：
10.1177/1536012116689499
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发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
Tian R
中科院分区：
文献类型：
--
作者：
Jiang C;Cai H;Peng X;Zhang P;Wu X;Tian R
甘露糖受体被认为是M2导向的肿瘤相关巨噬细胞（TAMs）的标志，但其在TAMs中的应用很少报道。为此，采用近红外染料Cy 7标记甘露糖受体的高亲和性配体脱氧甘露糖（DM），并在体内外评价其对TAMs靶向成像的可行性。合成Cy 7-DM，并评价其与体外诱导的TAM的结合亲和力、体内异种移植肿瘤小鼠模型中的全身成像以及解剖组织中的细胞定位。我们证明了在肿瘤组织中诱导的M2巨噬细胞和TAM对Cy 7-DM的高摄取。在体近红外实时成像中，Cy 7-DM成像在肿瘤病灶中显示了丰富的TAM，而不是炎症部位，并且在成像的1 - 8 h内，肿瘤中Cy 7-DM信号的数量显著高于炎症部位。我们的研究结果表明，甘露糖可以快速和特异性地靶向TAMs，是一个有希望的候选人，为靶向诊断的肿瘤与丰富的TAMs。
Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs), but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM), a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7), and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.